Hostname: page-component-848d4c4894-2pzkn Total loading time: 0 Render date: 2024-06-10T16:46:20.283Z Has data issue: false hasContentIssue false
  • English
  • Français

Use of the terminal complement inhibitor eculizumab in paediatric heart transplant recipients

Published online by Cambridge University Press:  26 December 2019

Yuk M. Law Open the ORCID record for Yuk M. Law [Opens in a new window] ,
Deipanjan Nandi ,
Kimberly Molina ,
Katheryn Gambetta ,
Kevin P. Daly  and
Bibhuti Das
Yuk M. Law*
Affiliation:
Division of Pediatric Cardiology, Seattle Children’s Hospital, Seattle, WA, USA
Deipanjan Nandi
Affiliation:
Cardiology, Nationwide Children’s Hospital, Columbus, OH, USA
Kimberly Molina
Affiliation:
Pediatric Cardiology, Primary Children’s Hospital, Salt Lake City, UT, USA
Katheryn Gambetta
Affiliation:
Pediatric Cardiology, Ann and Robert H Lurie Children’s Hospital, Chicago, IL, USA
Kevin P. Daly
Affiliation:
Department of Cardiology, Boston Children’s Hospital & Department of Pediatrics, Harvard Medical School, Boston, MA, USA
Bibhuti Das
Affiliation:
Department of Pediatric Cardiology, Baylor College of Medicine, Texas Children’s Hospital, Austin, TX, USA
*
Author for correspondence: Yuk M. Law, Division of Pediatric Cardiology, Seattle Children’s Hospital, Seattle, WA, USA. Tel: 206-987-1417; Fax: 206-987-3839; E-mail: yuk.law@seattlechildrens.org
Get access Rights & Permissions [Opens in a new window]

Abstract

Antibody-mediated rejection is a major clinical challenge that limits graft survival. Various modalities of treatment have been reported in small studies in paediatric heart recipients. A novel approach is to use complement-inhibiting agents, such as eculizumab, which inhibits cleavage of C5 to C5a thereby limiting the formation of membrane attack complex and terminal complement-mediated injury of tissue-bound antibodies. This medical modality of treatment has theoretical advantages but the collective experience in its use in the solid organ transplant community remains small. We add to this experience by combining 14 cases from 6 paediatric heart centres in this descriptive study.

Keywords

Heart transplantationeculizumabmedical therapyantiboby-mediated rejectionchildrenpaediatrics
Type
Original Article
Information
Cardiology in the Young , Volume 30 , Issue 1 , January 2020 , pp. 107 - 113
Copyright
© Cambridge University Press 2019

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Rossano, JW, Dipchand, AI, Edwards, LB, et al.The Registry of the International Society for Heart and Lung Transplantation: nineteenth pediatric heart transplantation report-2016; focus theme: primary diagnostic indications for transplant. J Heart Lung Transplant 2016; 35: 1185–1195.CrossRefGoogle ScholarPubMed
Gossett, JG, Canter, CE, Zheng, J, et al.Decline in rejection in the first year after pediatric cardiac transplantation: a multi-institutional study. J Heart Lung Transplant 2010; 29: 625–632.CrossRefGoogle ScholarPubMed
Kobashigawa, J, Crespo-Leiro, MG, Ensminger, SM, et al.Report from a consensus conference on antibody-mediated rejection in heart transplantation. J Heart Lung Transplant 2011; 30: 252–269.CrossRefGoogle ScholarPubMed
Thrush, PT, Pahl, E, Naftel, DC, et al.A multi-institutional evaluation of antibody-mediated rejection utilizing the pediatric heart transplant study database: incidence, therapies and outcomes. J Heart Lung Transplant 2016; 35: 1497–1504.CrossRefGoogle ScholarPubMed
Vaughn, GR, Jorgensen, NW, Law, YM, et al.Outcome of antibody-mediated rejection compared to acute cellular rejection after pediatric heart transplantation. Pediatr Transplant 2018; 22: e13081.CrossRefGoogle ScholarPubMed
Everitt, MD, Hammond, ME, Snow, GL, et al.Biopsy-diagnosed antibody-mediated rejection based on the proposed International Society for Heart and Lung Transplantation working formulation is associated with adverse cardiovascular outcomes after pediatric heart transplant. J Heart Lung Transplant 2012; 31: 686–693.CrossRefGoogle ScholarPubMed
Everitt, MD, Pahl, E, Schechtman, KB, et al.Rejection with hemodynamic compromise in the current era of pediatric heart transplantation: a multi-institutional study. J Heart Lung Transplant 2011; 30: 282–288.CrossRefGoogle ScholarPubMed
Colvin, MM, Cook, JL, Chang, P, et al.Antibody-mediated rejection in cardiac transplantation: emerging knowledge in diagnosis and management: a scientific statement from the American Heart Association. Circulation 2015; 131: 1608–1639.CrossRefGoogle ScholarPubMed
Olson, SR, Lu, E, Sulpizio, E, et al.When to stop Eculizumab in complement-mediated thrombotic microangiopathies? Am J Nephrol 2018; 48: 96–107.CrossRefGoogle ScholarPubMed
Berry, GJ, Burke, MM, Andersen, C, et al.The 2013 International Society for Heart and Lung Transplantation Working Formulation for the standardization of nomenclature in the pathologic diagnosis of antibody-mediated rejection in heart transplantation. J Heart Lung Transplant 2013; 32: 1147–1162.CrossRefGoogle ScholarPubMed
Geft, D, Kobashigawa, J.Current concepts for sensitized patients before transplantation. Curr Opin Organ Transplant 2017; 22: 236–241.CrossRefGoogle ScholarPubMed
Kobashigawa, J, Colvin, M, Potena, L, et al.The management of antibodies in heart transplantation: an ISHLT consensus document. J Heart Lung Transplant 2018; 37: 537–547.CrossRefGoogle ScholarPubMed
Patel, J, Dilibero, D, Kittleson, M, et al.Terminal complement inhibition for highly sensitized patients undergoing heart transplantation – doable? J Heart Lung Transplant 2015; 34: S31.CrossRefGoogle Scholar
Fishman, JA, Rubin, RH.Infection in organ-transplant recipients. NEJM 1998; 338: 1741–1751.CrossRefGoogle ScholarPubMed
Gómez-Cibeira, E, Ivanovic-Barbeito, Y, Gutiérrez-Martínez, E, et al.Eculizumab-related progressive multifocal leukoencephalopathy. Neurology 2016; 86: 399–400.CrossRefGoogle ScholarPubMed
Feingold, B, Webber, SA, Bryce, CL, et al.Comparison of listing strategies for allosensitized heart transplant candidates requiring transplant at high urgency: a decision model analysis. Am J Transplant 2015; 15: 427–435.CrossRefGoogle ScholarPubMed
Sapir-Pichhadze, R, Tinckam, KJ, Laupacis, A, et al.Immune sensitization and mortality in wait-listed kidney transplant candidates. J Am Soc Nephrol 2016; 27: 570–578.CrossRefGoogle ScholarPubMed
Mahle, WT, Tresler, MA, Edens, RE, et al.Allosensitization and outcomes in pediatric heart transplantation. J Heart Lung Transplant 2011; 30: 1221–1227.CrossRefGoogle ScholarPubMed
Webber, S, Zeevi, A, Mason, K, et al.Pediatric heart transplantation across a positive crossmatch: first year results from the CTOTC-04 multi-institutional study. Am J Transplant 2018; 18: 2148–2162.CrossRefGoogle ScholarPubMed
Stegall, MD, Diwan, T, Raghavaiah, S, et al.Terminal complement inhibition decreases antibody-mediated rejection in sensitized renal transplant recipients. Am J Transplant 2011; 11: 2405–2413.CrossRefGoogle ScholarPubMed
Kulkarni, S, Kirkiles-Smith, NC, Deng, YH, et al.Eculizumab therapy for chronic antibody-mediated injury in kidney transplant recipients: a pilot randomized controlled trial. Am J Transplant 2017; 17: 682–691.CrossRefGoogle ScholarPubMed
van den Brand, JA, Verhave, JC, Adang, EM, et al.Cost-effectiveness of eculizumab treatment after kidney transplantation in patients with atypical haemolytic uraemic syndrome. Nephrol Dial Transplant 2017; 32: i115–i122.CrossRefGoogle ScholarPubMed
Zahra, G, Ayvaci, MUS, Michael, H, et al.Cost-effectiveness of antibody-based induction therapy in deceased donor kidney transplantation in the United States. Transplantation 2017; 101: 1234–1241.Google Scholar